Project Abstract The current opioid use disorder (OUD) epidemic has resulted a rise in infections including not only HCV and HIV, but also invasive bacterial infections including Staphylococcus Aureus bacteremia, endocarditis, skin and soft tissue infections, and bone and joint infections. Persons admitted to hospitals with co-occurring OUD and related infections presents a critical time to intervene, both to improve infectious disease and opioid addiction outcomes. Most hospitals, particularly in under-resourced and rural areas, lack physicians trained in treatment of OUD, and standard care for patients even in busy academic urban hospitals typically consists of detoxification and referral to outpatient resources for follow-up treatment. This asks patients with severe OUD to tolerate withdrawal symptoms, risking premature exit from hospital, and relapse to opioid use after failure to connect with OUD treatment referrals. Results include long lengths of stay due to concern about relapse and non-adherence if patients leave the hospital, and readmissions after OUD relapse, lack of antibiotic adherence and reinfection, leading to both poor clinical outcome and high healthcare costs. Hospital settings that manage these infections are treating increasing numbers of people with untreated OUD. This provides an opportunity to engage patients in treatment of their OUD while managing their infections. Infectious Disease (ID) specialists and hospitalists are a critical and logical resource to build capacity and increase access to medication-assisted treatment (MAT). An injectable long-acting monthly formulation of buprenorphine (LAB) has a potential advantage for initiating OUD treatment within hospital settings and bridging to treatment after discharge to the community. We propose to test a new model of care (ID/LAB) in which opioid use disorder (OUD) is managed by ID specialists and hospitalists concurrent with management of the OUD-related infections, using long-acting injectable buprenorphine (LAB), followed by referral as soon as possible after hospital discharge to community resources for long term treatment of OUD. Adults admitted to a hospital for infections related to OUD (N = 200) will be identified at hospital admission and randomly assigned 1:1 to ID/LAB or treatment as usual (TAU), consisting of detoxification and referral to community-based treatment for OUD in parallel with treatment of the infectious disease. The primary outcome measure will be the proportion of patients enrolled in effective medication treatment for OUD (buprenorphine, methadone, or injection naltrexone) at 3 months (12 weeks) after randomization. Study sites will be three hospitals serving geographically diverse, mixed urban and rural communities across the Eastern U.S. With successful co- treatment of addiction and infectious diseases, OUD could be stabilized, while repeat infections are avoided, and risk of morbidity and mortality due to infection or overdose reduced.